Nerolidol pyrophosphate

Further biosynthetic studies by Cane et have shown that the conversion of farnesyl pyrophosphate (15) into nerolidyl pyrophosphate (16) proceeds by a net syn (suprafacial) process and that the subsequent cyclization to cyclonerodiol (17) occurs in a trans manner (Scheme 4). This careful piece of work was achieved by incorporation studies with doubly labelled nerolidol and mevalonate precursors and then by ascertaining the chirality of the acetate derived by Kuhn-Roth oxidation through enzymatic conversion (malate synthase/fumarase incubation) into labelled malate. In a subsequent series of experiments with labelled precursors, Cane et have confirmed that (i) only the C-7 hydroxy-group in cyclonerodiol is derived from water whereas the C-3 hydroxy-group is derived... 

Most acyclic sesquiterpenes are derived from famesol and nerolidol (7) or from the corresponding pyrophosphate esters. Although the number of acyclic sesquiterpenes is relatively small, Z- and -famesol (5 and 6), nerolidol (7), and the corresponding olefins are relatively common in essential oils. The famesenes and a few other compounds, such as 3-sinesal (8), are derived in a straightforward manner, but most acyclic sesquiterpenes are more complex in origin (Fig. 21.4). 

In order for cyclization of the intermediates to occur, the TT-orbitals of the relevant double bonds must be properly aligned to achieve the required geometry for interaction. This condition is met only if the individual double bonds of the allylic substrate are mutually perpendicular to a common plane. Further, C-1 to C-4 and the attached methyl group, C-15, are constrained to a common plane, as are C-5 to C-8 and C-14, and C9 to C-13. To cyclize, C-1 must be brought to within bonding distance of either the central or distal double bond with displacement of pyrophosphate from C-1 of famesyl pyrophosphate occurring with net anti stereochemistry (Cane, 1990). For those cases which require the intermediacy of an nerolidol pyrosphate-like intermediate, the allylic displacement of the pyrophosphate moiety will take place in an anti sense from a cisoid conformation (Cane, 1990). 

Figure 5.22 shows a tiny fraction of the biosynthetic pathways derived from (Z, )-famesyl pyrophosphate. Direct hydrolysis leads to acyclic sesquiterpenoids such as famesol (111) and nerolidol... 

From this compound, the series of reactions proceeds to form either the C20 compound (see Section 7) or the highly polymeric natural rubber (see Section 9), or it is terminated by a head to head condensation of two C16 units. The mechanism again includes an allylic rearrangement, farnesyl pyrophosphate to a nerolidol derivative, and an attack by a carbonium ion. A reduction step with NADPH2 finally forms squalene. 

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